DNA repair plays a critical role in protecting the genome from insults of
cancer-causing agents, such as those found in tobacco
smoke. Therefore, reduced DNA repair capacity can increase the susceptibility to smoking-related
cancers. Recently, several polymorphisms have been identified in the
xeroderma pigmentosum group G (XPG) gene, and it is possible that these polymorphisms may affect the DNA repair capacity, thereby modulating
cancer susceptibility. We investigated the relationship between the His1104Asp polymorphism in the XPG gene and the risk of
lung cancer. The study population consisted of 310
lung cancer patients and 311 healthy controls who were frequency (1:1) matched based on age and sex. The
Asp/Asp genotype was more frequent in the controls (28.9%) than in the cases (18.7%) and associated with a significantly decreased risk of
lung cancer [adjusted odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.37-0.80] when the combined
His/His and His/Asp genotype was used as the reference. The protective effect of the
Asp/Asp genotype against
lung cancer was statistically significant in the older subjects (adjusted OR = 0.51, 95% CI = 0.37-0.80), males (adjusted OR = 0.54, 95% CI = 0.35-0.83), and lighter smokers (adjusted OR = 0.48, 95% CI = 0.25-0.94) in a stratification analysis. When the
lung cancers were analyzed by histologic type, the
Asp/Asp genotype was associated with a significantly decreased risk of
squamous cell carcinoma (adjusted OR = 0.55, 95% CI = 0.34-0.88) and
small cell lung cancer (adjusted OR = 0.44, 95% CI = 0.20-0.97), but non-significant decreased risk of
adenocarcinoma (adjusted OR = 0.64, 95% CI = 0.36-1.12). These results suggest that the XPG
codon 1104 polymorphism contributes to
genetic susceptibility to
lung cancer.